Non HFE related hereditary haemochromatosis.

Hereditary hemochromatosis (HH) is manifested as iron overload in different organs due to homozygosity of a single autosomal mutation. Two different mutations C282Y and H63D in the HFE gene have been associated with hereditary hemochromatosis cases. This disease is seen in northern european populations, but in India it is a rare disease. We report a young male with severe abnormalty of liver functions due to Non HFE related Hereditary Hemochromatosis.

In silico comparative analysis of LRRK2 interactomes from brain, kidney and lung.

Mutations in LRRK2 are the most frequent cause of familial Parkinson's disease (PD), with common LRRK2 non-coding variants also acting as risk factors for idiopathic PD. Currently, therapeutic agents targeting LRRK2 are undergoing advanced clinical trials in humans, however, it is important to understand the wider implications of LRRK2 targeted treatments given that LRRK2 is expressed in diverse tissues including the brain, kidney and lungs. This presents challenges to treatment in terms of effects on peripheral organ functioning, thus, protein interactors of LRRK2 could be targeted in lieu to optimize therapeutic effects. Herein an in-silico analysis of LRRK2 direct interactors in brain tissue from various brain regionswas conducted along with a comparative analysis of the LRRK2 interactome in the brain, kidney, and lung tissues. This was carried out based on curated protein-protein interaction (PPI) data from protein interaction databases such as HIPPIE, human gene/protein expression databases and Gene ontology (GO) enrichment analysis using Bingo. Seven targets (MAP2K6, MATK, MAPT, PAK6, SH3GL2, CDC42EP3 and CHGB) were found to be viable objectives for LRRK2 based investigations for PD that would have minimal impact on optimal functioning within peripheral organs. Specifically, MAPT, CHGB, PAK6, and SH3GL2 interacted with LRRK2 in the brain and kidney but not in lung tissue whilst LRRK2-MAP2K6 interacted only in the cerebellum and MATK-LRRK2 interaction was absent in kidney tissues. CDC42EP3 expression levels were low in brain tissues compared to kidney/lung. The results of this computational analysis suggest new avenues for experimental investigations towards LRRK2-targeted therapeutics.

Discovery of Novel Soluble Epoxide Hydrolase Inhibitors as Potent Vasodilators.

In view of the role of sEH (soluble epoxide hydrolase) in hypertension, we have developed a rigorously validated pharmacophore model containing one HBA (Hydrogen Bond Acceptor), two HY (Hydrophobic) and one RA (Ring Aromatic) features. The model was used as a query to search the NCI (National Cancer Institute) and Maybridge database leading to retrieval of many compounds which were sorted on the basis of predicted activity, fit value and Lipinski's violation. The selected compounds were docked into the active site of enzyme soluble epoxide hydrolase. Potential interactions were observed between the features of the identified hits and the amino acids present in the docking site. The three selected compounds were subjected to in vitro evaluation using enzyme- based assay and the isolated rat aortic model followed by cytotoxicity studies. The results demonstrate that the identified compounds are potent, safe and novel soluble epoxide hydrolase inhibitors.

In Vivo Assessment of Choroid in Diabetic Retinopathy by Enhanced Depth Imaging in Spectral Domain Optical Coherence Tomography.

PURPOSE: The aim of this study was to measure the largest hyporeflective (LHR) lumen in the choroid and subfoveal choroidal thickness (SFCT) in patients with diabetic retinopathy (DR) and in control subjects using enhanced depth imaging (EDI) spectral domain optical coherence tomography (SD-OCT). DESIGN: This was a prospective, cross-sectional study. METHODS: This was a study of 240 eyes of DR patients (n = 120) and control subjects (n = 120) matched for age, sex, and refractive error. The LHR lumens of the choroidal vessels and SFCT were measured by EDI SD-OCT. Further intergroup classification into nonproliferative and proliferative DR, with or without macular edema, was done. RESULTS: The mean diameter of the LHR lumen in DR patients (139.24 ± 35.53 µm) was significantly smaller (P < 0.01) than in control subjects (186.37 ± 26.43 µm). The mean SFCT was also significantly less (P < 0.01) in patients with diabetes (277.15 ± 32.24 µm) as compared with control subjects (313.68 ± 25.13 µm). There was no significant intergroup variation. CONCLUSIONS: Patients with DR showed smaller LHR lumen and SFCT as compared with control eyes. In vivo assessment of the choroid in DR is possible using EDI SD-OCT.

Correlation of spectral domain optical coherence tomography findings in sub-silicone oil foveal depression space and visual outcome in eyes undergoing silicone oil removal.

BACKGROUND/PURPOSE: To describe small hyper-reflective spherical bodies in sub-silicone oil-foveal depression (SSO-FD) space using spectral domain optical coherence tomography (SD-OCT) and its effect on visual outcomes in eyes undergoing silicone oil removal (SOR). METHODS: This was a prospective interventional comparative study comprising 42 eyes undergoing SOR with clear media. All patients underwent detailed clinical examination and SD-OCT scan of fovea pre-operatively and at 30 days and 90 days postoperatively. Patients were divided into Group A (n = 21) and Group B (n = 21) depending on presence or absence, respectively, of small hyper-reflective spherical bodies in the SSO-FD space in preoperative scans. The findings between SD-OCT and best-corrected visual acuity were correlated and analyzed. RESULTS: The mean age of patients was 41.9 years (range, 23-60 years) in Group A and 45.6 years (range, 23-60 years) in Group B. Twenty-one eyes showed small hyper-reflective spherical bodies on SD-OCT imaging. These were thought to represent emulsified silicone oil globules trapped in the potential space created by silicone oil meniscus and foveal pit, which is the SSO-FD space. These bodies were absent in all post SOR scans of Group A and Group B. Group A had significant visual improvement (p = 0.0001) after SOR with clearance of these hyper-reflective bodies as compared to Group B(p = 0.356). CONCLUSION: We conclude that these small hyper-reflective spherical bodies in the SSO-FD space were most likely emulsified silicone oil globules and correlated with significant visual improvement with their clearance after silicone oil removal.